Preterm birth is defined as delivery before 37 completed week’s gestation. The World Health Organisation defines the different stages of preterm delivery as follows:
- Extreme preterm: before 28 weeks
- Very preterm: 28 to 32 weeks
- Moderate to late preterm: 32 to 37 weeks
Around 15 million babies are born each year before 37 completed weeks of gestation, and this number is reported to be rising . Approximately 60% of these births are in Africa and South Asia ,however this is also a problem in high income countries such as the UK. Around 60,000 babies are born prematurely in the UK annually .
Prematurity also remains the number one cause of neonatal death globally, and the number one cause of death in under five year olds . Morbidity and mortality rates vary greatly depending upon several factors including gestation, birth weight and whether or not the infant was born in a high vs. low income country. This will be discussed in more detail later in the article.
There are many overlapping causes that can be attributed to premature delivery:
- Around 25% of preterm deliveries are planned due to life threatening conditions affecting either the mother or foetus (pre-eclampsia, renal disease, severe growth restriction etc)
- Approximately 30-40% are due to premature or prelabour rupture of membranes
- Around 25% are due to an emergency event such as placental abruption, eclampsia or severe infection
- Roughly 40% of the cases have no identifiable cause
There are several identified risk factors for premature delivery including (but not limited to) :
- Previous preterm delivery
- Multiple pregnancy
- Smoking and illicit drug use in pregnancy
- Being under or overweight in pregnancy
- Early Pregnancy (within 6 months of previous pregnancy)
- Problems involving cervix, uterus or placenta, including infection
- Certain chronic conditions such as diabetes and hypertension
- Physical injury/trauma
Typically, the history of a premature delivery is clear and brief. There will usually be an obstetric record of estimated due date (and therefore estimated gestation) if a woman presents in labour. However, there are cases such as with a concealed or unknown pregnancy, where antenatal care may not have been accessed, and an assessment of gestational age needs to be made by a clinician.
The date of the woman’s last menstrual period can be used to estimate an expected gestational age but if this is not known (or the woman is uncertain), clinical examination can be used to evaluate the infant. This is done roughly after 24 hours, to allow stabilization of the patient and adequate neurological examination.
Routine examination of the preterm baby does not differ a lot from our general approach. However, certain precautions need to happen in order to avoid hypothermia, and minimize handling.
The Dubowitz/Ballard Examination for gestational age is an example of an assessment tool which can be used to estimate neonatal maturity [4,5,6]. It uses a combination of external physical and neuromuscular features to determine a score. This is then used to give an estimate of a 2 week window of gestation.
Physical features assessed include skin, lanugo (thin, soft hairs), and eye, ear and genital formation. Neuromuscular assessment looks at areas such as posture and arm recoil.
Following stabilization and transfer to the neonatal unit, there are several baseline investigations that most premature infants might require during their stay, tailored to each individual patient.
- Blood gas – This is commonly used to help assess the respiratory and metabolic state of the infant and increase or decrease support as needed
- Full blood count – Preterm infants are at high risk of infection, thrombocytopenia and anaemia, therefore requiring close observation of their WCC, platelets and RBC
- Urea, creatinine and electrolytes – Many units do not perform renal function tests at initial admission, as this is more likely to be reflective of the mother’s electrolyte balance roughly for the first 24 hours of life. However, electrolyte and fluid balance is paramount for neonatal care and close monitoring of renal function helps to tailor management accordingly
- Blood culture – infection can be a risk factor in preterm delivery therefore frequently infants are screened with a blood culture on admission and commenced on intravenous antibiotics. If the baby becomes unwell, they would likely be re-screened as per local protocols.
- CRP – In view of the association between prematurity and infection, CRP is checked on admission, and monitored during the child’s stay on the neonatal unit. There is a wide range of protocols for this. NICE guidelines also exist suggesting level thresholds for investigations such as LP . Also, preterm infants are at risk of developing infections for many reasons including immature immune systems, multiple invasive procedures and in dwelling central lines to name a few.
- Blood group and Direct Coombs Test/ Direct Antiglobulin Test (DCT/DAT) – Many premature infants require a blood transfusion during their stay in the neonatal unit. Almost all (approximately 80%) will develop jaundice in the first week of life. These tests should be checked with admission bloods.
Imaging or invasive tests
- Chest x-ray – Almost all infants born before 32 weeks will need some form of respiratory support. A chest x-ray is needed if an infant shows signs of respiratory distress (tachypnoea, oxygen dependency, increased work of breathing). If a baby is intubated and ventilated, a chest x-ray is required to assess the position of the endotracheal tube.
- Abdominal x-ray – Preterm infants are often in need of parenteral nutrition and several intravenous infusions in the first few days and weeks of life. Therefore, central venous and arterial access are usually inserted through the umbilical vein and arteries. An abdominal and chest x-ray are used to assess the position of the umbilical venous and umbilical arterial catheters after insertion. Preterm infants are also at risk of developing necrotising enterocolitis. If this is suspected, an AP and lateral film may be needed to assess for signs of perforation (free air within the abdominal cavity, football sign, pneumatosis intestinalis, immobile bowel loops in repeat x-rays).
- Cranial ultrasound scan (CrUSS) – The brains of preterm and very low birth weight infants are at increased risk of neurological insults from haemorrhagic, ischaemic and infective factors. CrUSS is used routinely in infants born at less than 32 weeks to assess for any signs of intraventricular haemorrhage or ischaemic periventricular white matter damage. It has the benefit of being a simple bedside tool which, when used repeatedly and in conjunction with other factors, can help identify those infants most at risk of adverse neurodevelopmental outcomes [8,9, 10]. This needs to be reviewed with an MRI at a later stage  .
Initial management begins antenatally if there is a threat of preterm delivery identified. The delivery of an extremely preterm infant should be planned for a hospital with a tertiary level neonatal unit. Antenatal transfer may be necessary or, if this is not possible, postnatal stabilisation and transfer needs to be arranged.
The obstetric team should administer a course of antenatal steroids. This has been shown to reduce the risk of death, IVH, and RDS in infants . Magnesium sulphate should also be offered as this has shown to be neuroprotective to the baby [13, 14]. See current NICE guidelines for more information .
In ideal circumstances, parents should be counselled by a senior member of the neonatal team prior to delivery and given the opportunity to visit the neonatal unit. There should be time for parents to assimilate information and ask questions. Unfortunately, this is often not possible due to the time critical nature of delivery.
There is much debate surrounding resuscitation of extreme preterm infants. Current guidelines suggest that if a woman presents in labour at a gestation of:
- Less than 23 weeks then resuscitation should not be performed
- Between 23 and 23+6 weeks then there may be a decision not to start resuscitation in the best interests of the baby, especially if parents have expressed this wish.
- Between 24 and 24+6 weeks, resuscitation should be commenced unless the baby is thought to be severely compromised. Response to initial measures should be considered before the decision is made to commence intensive care.
- After 25 weeks, it is appropriate to resuscitate and start intensive care.
See BAPM guidelines for more details .
The newborn life support algorithm can be found here  from the resuscitation council or for more information attend an NLS course.
Preterm infants require a senior member of the team in attendance. Preterm infants also need extra help maintaining temperature therefore a plastic wrap and/or heating mattress can be used in combination with the overhead heat lamp.
After delivery, stabilisation and initial management, the care of an extreme preterm infants is complex. All organ systems are immature and require some level of assistance. This varies depending upon many factors including gestation, birthweight and other co-morbidities of the infant and mother.
Table 1 is a simple system based summary of this management (be aware there is some overlap, and that this not exhaustive, aiming only to provide a brief insight into the complexity of managing preterm infants)
|Respiratory||Respiratory distress syndrome, Surfactant deficient lung disease, Chronic lung disease/ Bronchopulmonary dysplasia, recurrent apnoea||Exogenous surfactant administration, endotracheal intubation and mechanical ventilation, Bilevel positive airway pressure, continuous positive airway pressure, high flow oxygen, nasal cannula low flow oxygen, ambient incubator oxygen, caffeine administration|
|Cardiovascular||Hypotension, perfusion abnormalities, PDA||Inotrope infusions (including dopamine, dobutamine, adrenaline, and noradrenaline), fluid management, ibuprofen or indomethacin administration, ligation of PDA (rare)|
|Neurological||Intraventricular haemorrhage, seizures, post haemorrhagic ventricular dilatation, neurodevelopmental delay, cerebral palsy. More below||Regular surveillance with CrUSS, regular head circumference measurement, administration of antiepileptic drugs (phenobarbital and phenytoin), referral to neurosurgical team if needed, long term neurodevelopmental follow up and support as necessary, awareness of level of stimulation (handling, noise, light, etc)|
|Gastrointestinal||Immature gut causing feed intolerance, necrotising enterocolitis (NEC)||Total parenteral nutrition (TPN), nasogastric and orogastric feeds, maternal and donor expressed breast milk, feeding protocols, antibiotic therapy and surgical review if NEC is suspected|
|Renal/electrolyte||Immature renal function||Close monitoring of fluid and electrolyte balance, electrolyte supplements when indicated, catheterisation if indicated|
|Metabolic||Jaundice, hyperglycaemia, hypoglycaemia, Inborn errors of metabolism||Phototherapy, exchange transfusion, insulin infusion, increase concentration or volume of glucose given via central IV access, baseline metabolic investigations (including Guthrie Card)|
|Infection/immune||Sepsis, increased risk of infection due to central lines and multiple procedures||Septic screen, intravenous antibiotic therapy according to local guidelines|
|Skin||Immature skin barrier leading to increased insensible losses and increased risk of infection||Nursing in a warm, humid incubator, aseptic non-touch technique during procedures|
|Thermoregulation||Immature thermoregulation||Nursing in a warm humid incubator, cot warmer, awareness of exposure whilst performing procedures and examinations|
|Eyes||Retinopathy of prematurity||Avoid excessive oxygen exposure, screening for retinopathy of prematurity by ophthalmology team, laser treatment if indicated|
Complications and Prognosis
Many of the complications associated with premature birth are briefly outlined above. It is beyond the scope of this article to go into each condition in detail. However, it is important to include an overview of information gained from the EPICure 1995 and EPICure 2 studies [18, 19] surrounding survival rates and neurodevelopmental outcomes.
Survival is rare before 23 weeks, but by 26 weeks, 3 out of 4 babies are expected to survive and by 27 weeks this figure is around 90%.
The earlier a baby is born, the higher the likelihood that they will have some neurodevelopmental impairment. Impairment can include gross motor delay, fine motor impairment, speech and language delay, learning and behavioural difficulties.
The 3-year follow-up of the EPICure 2 study has shown that, of infants born at 22 weeks, around 1/3 will have no or mild disability. By 26 weeks this increases to around 75%. It was found that around 2/3 of the infants seen in the EPICure study required some support at school, although only 1/8 required attendance at a special school.
This information is important when counselling parents.
Delivery of a preterm infant can cause a mix of emotions for parents and the wider family. It is a time of many ups and downs and support is essential in helping families deal with the stress and unpredictability of having a premature baby.
From an early stage parents, should be invited to be involved in the care of their infant and when the baby is stable enough, periods of kangaroo care/skin-to-skin should be encouraged. There are often local support groups available for parents and charities such as Bliss  that offer information and support to families of preterm and sick infants.
End of life care and ethical considerations
Neonatology is a complex, challenging and highly emotive field of medicine. There are unfortunately times when the decision is made to “withdraw” intensive care. End of life care is an important aspect of neonatal medicine.
For guidance surrounding withdrawal of life sustaining treatment please see references [21, 22]. It is beyond the scope of this article to debate ethical dilemmas in any detail. For those interested, the Nuffield Council on Bioethics produced an extensive report in 2006 .
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1st Draft: Dr Frances Callaghan
Senior reviewer: Dr Umberto Piaggio (Senior neonatal registrar)